Our provocative results measuring the kinetics of surfactant phospholipid metabolism in perinatal rabbits and using natural surfactant for the treatment of the respiratory distress syndrome (RDS) in prematurely delivered sheep can be extended by a thorough analysis of phospholipid metabolism in the sheep throughout development. All studies will be conducted in vivo to define both the normal physiology of surfactant phospholipids and how respiratory distress may modify this physiology. Using different labeled phospholipid precursors and the chronically catherized fetal sheep model, term newborn lambs, and adult sheep, we will measure the appearance of the labeled phospholipids, phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine plus phosphatidylserine, into the microsomes, lamellar bodies and alveolar space. The difference between subcellular and the alveolar phospholipid metabolism with development will be defined. Changes in the composition of the surfactant phospholipids with development will also be identified. Twin premature lambs will be delivered by cesarean section at approximately 120 days, placed on ventilators, and treated for RDS. One lamb will receive radioactive natural surfactant and the other will be the untreated control. Both lambs also will receive a labeled phospholipid precursor at the time of birth. The labeling and turnover of both exogenously synthesized and endogenously administered surfactant phospholipids in lung subcellular fractions (microsomes and lamellar bodies) and the aveolar wash will be measured and compared. Survival data, blood gas analysis, an pressure-volume measurements on the lungs will be made.